What
happens to the body in extreme climates is of great interest to the military.
One of the risks soldiers may face is oxygen deprivation, which can kill
cells and damage vital organs. With the ultimate goal of helping military
men and women survive stressful conditions, U.S. Army researchers and
their colleagues have used genomics to study how liver cells respond to
the loss of oxygen.

U.S. Army scientists are using genomics to study ways to protect soldiers from the harmful effects of high altitude...

In a new study, they identify nearly 390 genes that switch on or off
in the absence of oxygen, or hypoxia.

The list of genes represents a first step in understanding how the human
body withstands harsh climates. Further research may benefit not only
the military but also civilians, including patients who receive donated
organs. During transplant surgery, the supply of oxygen to the organ is
temporarily cut off, and understanding the stress response could lead
to new ways to protect them from damage.

"It would be great if we could find out what makes an organ resistant
to hypoxia, and then promote that before cutting off its oxygen supply
and transplanting it," says Lt. Col. Larry Sonna of the U.S. Army
Research Institute of Environmental Medicine in Natick, Massachusetts,
who led the study. The institute conducts research on how environment,
climate and nutrition affect the health and performance of military personnel.

"This research is really quite important for understanding what
happens to someone who becomes critically ill," says Craig Lilly,
a critical care specialist at Harvard Medical School in Boston and co-author
of the study. Doctors in the intensive care unit deal with patients whose
cells are starving for oxygen "almost on a daily basis," Lilly
says.

...and extreme heat. Images courtesy of Lt. Col. Larry Sonna and
the U.S. Army Research Institute of Environmental Medicine, Natick,
Mass.

As oxygen levels drop, genes involved in the cell's suicide response
switch on, the researchers found. Some of these genes could be altered
to make tissue more tolerant to hypoxia, says Lilly, who also directs
the medical intensive care unit at Boston's Brigham and Women's Hospital.

The new findings seem to contradict long-held dogma among scientists
that cells respond the same way to different environmental stressorsfrom
extreme heat to bitter cold. "There is a certain degree of specialization
in human cells in responding to stress," says Sonna, whose group
reports their findings in Physiological Genomics.

In the study, liver cells were exposed to air with one percent oxygen
(Earth's atmosphere is 21 percent oxygen). That level simulates what cells
experience during critical illness or ascent to high altitudes. It is
also low enough to trigger a cell's defense mechanism against hypoxia.

The researchers identified the genes using 'gene chip' technology. Gene
chips are glass slides or microchips spotted with thousands of fragments
of DNA. A single chip can reveal which genes in a cell are active under
specific conditions.

Future studies will need to sort out which genes are really involved
in the stress response, and which ones aren't. The analysis of thousands
of genes inevitably leads to false positives. As with any study, says
Sonna, the key will be replicating the results in other laboratories and
different conditions.